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Synlett 2010(4): 672-674  
DOI: 10.1055/s-0029-1219337
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Expedient Route to an Amine Precursor of Halichlorine and Pinnaic Acid from Nitrocyclopent-1-ene

Brett Stevenson, William Lewis, James Dowden*
School of Chemistry, University of Nottingham, University Park, Nottingham, NG7 2RD, UK
Fax: +44(115)9513564; e-Mail: james.dowden@nottingham.ac.uk;
Further Information

Publication History

Received 10 November 2009
Publication Date:
19 January 2010 (online)

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Abstract

Diastereoselective addition of n-propanal to nitrocyclopent-1-ene, aldehyde protection, 1,6-conjugate addition, and cross metathesis provides a facile route to key amine precursors of halichlorine and pinnaic acid.

Key words

nitroalkene - organocatalysis - conjugate addition - ­alkene metathesis

    References and Notes

  • 1a Trauner D. Schwarz JB. Danishefsky SJ. Angew. Chem. Int. Ed.  1999,  38:  3542 
    Google Scholar
  • 1b Carson MW. Kim G. Danishefsky SJ. Angew. Chem. Int. Ed.  2001,  40:  4453 
    Google Scholar
  • 1c Christie HS. Heathcock CH. Proc. Natl. Acad. Sci. U.S.A.  2004,  101:  12079 
    Google Scholar
  • 2 Clive DLJ. Yu ML. Wang J. Yeh VSC. Kang SZ. Chem. Rev.  2005,  105:  4483 
    CrossrefPubMedGoogle Scholar
  • 3a Xu S. Arimoto H. Uemura D. Angew. Chem. Int. Ed.  2007,  46:  5746 
    Google Scholar
  • 3b Wu H. Zhang HG. Zhao G. Tetrahedron  2007,  63:  6454 
    Google Scholar
  • 3c Liu DZ. Acharya HP. Yu ML. Wang J. Yeh VSC. Kang SZ. Chiruta C. Jachak SM. Clive DLJ. J. Org. Chem.  2009,  74:  7417 
    Google Scholar
  • 4a Kim H. Seo JH. Shin KJ. Kim DJ. Kim D. Heterocycles  2006,  70:  143 
    Google Scholar
  • 4b Caprio V. Synlett  2007,  1219 
    Google Scholar
  • 4c Clive DLJ. Li ZY. Yu ML. J. Org. Chem.  2007,  72:  5608 
    Google Scholar
  • 4d Hurley PB. Dake GR. J. Org. Chem.  2008,  73:  4131 
    Google Scholar
  • 4e Keck GE. Heumann SA. Org. Lett.  2008,  10:  4783 
    Google Scholar
  • 4f Wang LH. Prabhudas B. Clive DLJ. J. Am. Chem. Soc.  2009,  131:  6003 
    Google Scholar
  • 4g Yamamoto Y. Yasuda Y. Nasu H. Tomioka K. Org. Lett.  2009,  11:  2007 
    Google Scholar
  • 4h Yang SH. Clark GR. Caprio V. Org. Biomol. Chem.  2009,  7:  2981 
    Google Scholar
  • 4i Amordea SM. Jewetta IT. Martin SF. Tetrahedron  2009,  65:  3222 
    Google Scholar
  • 5 Andrey O. Vidonne A. Alexakis A. Tetrahedron Lett.  2003,  44:  7901 
    CrossrefGoogle Scholar
  • 6a Risaliti A. Forchiassin M. Valentin E. Tetrahedron  1968,  24:  1889 
    Google Scholar
  • 6b Chinchilla R. Bäckvall JE. Tetrahedron Lett.  1992,  33:  5641 
    Google Scholar
  • 6c Denmark SE. Thorarensen A. Chem. Rev.  1996,  96:  137 
    Google Scholar
  • 6d Diez D. Gil MJ. Moro RF. Marcos IS. Garcia P. Basabe P. Garrido NM. Broughton HB. Urones JG. Tetrahedron  2007,  63:  740 
    Google Scholar
  • 6e Domingo LR. Picher MT. Arroyo P. Eur. J. Org. Chem.  2006,  2570 
    Google Scholar
  • 7 Corey EJ. Estreicher H. J. Am. Chem. Soc.  1978,  100:  6294 
    CrossrefGoogle Scholar
  • 10 Maki K. Kania M. Shibasaki M. Tetrahedron  2007,  63:  4250 
    CrossrefGoogle Scholar
  • 11 Wade PA. Morrow S. Hardinger S. J. Org. Chem.  1982,  47:  365 
    CrossrefGoogle Scholar
  • 12 Bernardi L. Cantarero-Lopez J. Jesus B. Jørgensen KA. J. Am. Chem. Soc.  2007,  129:  5772 
    CrossrefPubMedGoogle Scholar
  • 13 Garber SB. Kingsbury JS. Gray BL. Hoveyda AH. J. Am. Chem. Soc.  2000,  122:  8168 
    Google Scholar
8

Cambridge Crystallographic Data Centre deposition numbers: 6a: 753693; 6b: 753694.

9

Schemes reflect the stereochemical orientation in the crystal structures for convenience of the reader. In fact, the opposite absolute stereochemistry is required for 1 and 2.

14

Data for Selected CompoundEthyl ( E )-5-{2-[1-(1,3-dioxan-2-yl)ethyl]-1-nitrocyclo-pentyl}pent-3-enoate (11)
(2E)-Ethyl-2,4-pentadienoate (0.50 g, 4.0 mmol) was added to of 2-[1-(2-nitrocyclopentyl)ethyl]-1,3-dioxane (5a, 0.83 g, 3.6 mmol), Cs2CO3 (1.33 g, 3.6 mmol), TBAI (0.06 g, 5 mol%) in xylene (70 mL) and CHCl3 (10 mL) and stirred at r.t. for 16 h. Water (100 mL) was added and the mixture extracted with EtOAc (3 × 60 mL). The organic layers were washed with brine (100 mL), dried (MgSO4), filtered, and concentrated. The crude material was purified by silica gel chromatography using PE-EtOAc (95:5) as eluent to give the ester 11 as a colourless oil (1.13 g, 88%). IR (CHCl3): ν = 2976, 1729, 1531, 1470, 1428, 1372, 1280, 1155 cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 5.72 (1 H, dt, J = 15.4, 6.8 Hz CH=CHCH2CO2Et), 5.50 (1 H, ddd, J = 15.4, 7.6, 6.8 Hz, CH=CHCH2CO2Et), 4.38 (1 H, d, J = 4.0 Hz, CHO2), 4.15 (2 H, q, J = 7.2 Hz, CH 2CH3), 4.14-4.08 [2 H, m, (OCH a Hb)2], 3.79-3.70 [2 H, m, (OCHa H b)2], 3.12 (1 H, dd, J = 14.4, 6.8 Hz, CCH a HbCH=CH), 3.05 (2 H, d, J = 6.8 Hz, CH2CO2Et), 2.52-2.44 (1 H, m, CHCNO2), 2.38 (1 H, dd,
J = 14.4, 7.6 Hz, CCH a H b CH=CH), 2.32-2.65 [1 H, m, CCH aHbCH2)2], 2.10-1.58 [7 H, m, CHCH(CH 2)2CHa H bCNO2,
(OCH2)CH aHb], 1.36-1.31 [1 H, m, (OCH2)CHa H b], 1.27 (3 H, t, J = 7.2 Hz, CH2CH 3), 0.73 (3 H, d, J = 7.2 Hz, CHCH 3) ppm. (100 MHz, CDCl3): δ = 171.6, 128.0, 127.3, 104.3, 99.4, 66.9, 66.8, 60.7, 49.2, 40.0, 38.1, 35.9, 35.1, 26.6, 25.8, 22.2, 14.2, 10.8 ppm. HRMS: m/z calcd for C18H30NO6: 356.2068; found: 356.2062 [M + H]+. Anal. Calcd for C18H29NO6: C, 60.80; H, 8.17; N, 3.94. Found: C, 61.10; H, 8.28; N, 3.69.

15

Data for Selected Compound tert -Butyl ( E )-4-{1-amino-2-[1-(1,3-dioxan-2-yl)ethyl]-cyclopentyl}but-2-enoate (14) Methyl (E)-4-{2-[1-(1,3-dioxan-2-yl)ethyl]-1-nitrocyclopentyl}but-2-enoate (12, 0.05 g, 0.14 mmol), Zn dust (0.18 g, 2.71 mmol), and HCl (1 M, 1.30 mL, 1.35 mmol) was stirred in i-PrOH (2 mL) overnight at r.t. 1 M KOH was added to the reaction until pH >11, then extracted with EtOAc (4 × 10 mL). The organic layers were dried (Na2SO4), filtered, and concentrated to yield amine 14 as a clear oil (0.04 g, 80%). IR (CHCl3): ν = 3010, 2976, 1704, 1449, 1392, 1369, 1240, 1154 cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 6.96 [1 H, ddd, J = 15.6, 8.4, 7.2 Hz, CH=CHCO2(CH 3)3], 5.86 [1 H, dt, J = 15.6, 1.2 Hz, CH=CHCO2(CH 3)3], 4.43 (1 H, d, J = 3.6 Hz, CHO2), 4.16-4.11 [2 H, m, (OCH a Hb)2], 3.79-3.72 [2 H, m, (OCHa H b)2], 2.50 (1 H, ddd, J = 13.6, 8.4, 1.2 Hz, CH a HbCH=CH), 2.32 (1 H, ddd, J = 13.6, 7.2, 1.2 Hz, CHa H b CH=CH), 2.13-2.00 [1 H, m, (OCH2)CH aHb], 1.87-1.35 [18 H, m, CHCH(CH 2)3, (OCH2)CHa H b, CO2(CH 3)3], 0.99 (3 H, d, J = 7.2, CHCH 3) ppm. ¹³C NMR (100 MHz, CDCl3): δ = 165.9, 144.9, 125.7, 105.3, 80.1, 67.0, 66.9, 62.0, 47.6, 44.9, 40.3, 37.0, 28.2, 27.8, 25.9, 22.5, 13.5 ppm. HRMS: m/z calcd for C19H34NO4: 340.2482; found: 340.2492 [M + H]+; m/z calcd for C19H34NO4Na: 362.2302; found: 362.2303 [M + Na]+.